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The distinctive feature of the mammalian brain is the large proportion occupied by the neocortex, which, in humans, represents as high as 90% of the total brain surface. Cortical circuitries, similar to other neuronal circuitries, undergo a fast increase in spine number in the early stages of life (peaking ...

The distinctive feature of the mammalian brain is the large proportion occupied by the neocortex, which, in humans, represents as high as 90% of the total brain surface. Cortical circuitries, similar to other neuronal circuitries, undergo a fast increase in spine number in the early stages of life (peaking about 9 years of age in humans; Petanjek et al. 2011), and then a phase of synaptic pruning and stabilization. Apart from learning-associated changes in fine spine morphology, it is generally believed that no major morphological change takes place in the adult brain and that the general organization and connectivity of brain circuitry remains quite stable throughout adulthood. A well-known exception to this general framework is provided by the major reorganization of the somatosensory cortex following elimination or inactivation of peripheral sensory inputs (reviewed by Kaas et al. 1983; Buonomano and Merzenich 1998). While this general picture is well established, a large amount of data is quickly accumulating showing that the brain undergoes important reorganization in adulthood even in the absence of sensorial deprivation, but in response to a multiplicity of physiological and pathological events such as stress, pain, or drug use. Such essentially functional events have been shown to lead to major cortical remodeling that exceeds the simply functional events and include morphological changes and connection rewiring.
Here we focus our attention on the reorganization of the prefrontal cortex in adult mammals. The prefrontal cortex is an eminently associative area, involved in high-order cognitive and emotional functions including attention, decision making, goal-directed behavior, and working memory, and which receives only minimal primary sensory input. Yet, this area shows remarkable adult plasticity. We examine this topic using multiple approaches ranging from the fine molecular detail of spine number and structure and electrophysiological neuronal properties, to the in vivo imaging in animals and humans. We discuss the general impact of such reorganization on our understanding of neuronal function as well as the direct or indirect implications for major pathologies such as clinical depression, schizophrenia and chronic pain.

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